Dr Muhammad Jamaluddin

Dr Muhammad Jamaluddin

Lecturer

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

I graduated with a degree double majoring in Biomedical Sciences and Microbiology and first class honours in Microbiology from the University of Queensland (UQ), Australia. I was awarded UQ international postgraduate research scholarship in 2011 to pursue my doctoral studies specializing in Protein Biochemistry at the School of Chemistry Molecular Biosciences, UQ. During my doctoral studies, I learnt and developed new methodologies in glycoproteomics in Dr Benjamin Schulz lab (NHMRC Career Development Fellow). In 2016, I joined Dr Pradeep Tanwar lab (ARC Future Fellow, Cancer Institute NSW Career Development Fellow and international leader on gynaecological cancer research) at the School of Biomedical Sciences and Pharmacy, the University of Newcastle, Australia. I am an early career researcher and was recently awarded with a John Hunter Hospital Charitable Trust project grant 2017 to advance my project. The major focus is to explore the mechanistic function of extracellular matrix in uterine leiomyogenesis.

Qualifications

  • PhD (Biochemistry), University of Queensland

Keywords

  • Glycosylation
  • Medical Biochemistry
  • Proteomics

Professional Experience

UON Appointment

Title Organisation / Department
Lecturer University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (6 outputs)

Year Citation Altmetrics Link
2017 Ko Y-A, Jamaluddin M, Adebayo M, Bajwa P, Scott R, Dharmarajan A, et al., 'Extracellular Matrix (ECM) Activates ß-catenin Signaling in Uterine Fibroids.', Reproduction, (2017)
DOI 10.1530/REP-17-0339
Co-authors Pradeep Tanwar, Rodney Scott
2014 Jamaluddin MFB, Bailey UM, Schulz BL, 'Oligosaccharyltransferase subunits bind polypeptide substrate to locally enhance N-glycosylation', Molecular and Cellular Proteomics, 13 3286-3293 (2014)

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine-linked glycosylation of ... [more]

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Oligosaccharyltransferase is a multiprotein complex that catalyzes asparagine-linked glycosylation of diverse proteins. Using yeast genetics and glycoproteomics, we found that transient interactions between nascent polypeptide and Ost3p/Ost6p, homologous subunits of oligosaccharyltransferase, were able to modulate glycosylation efficiency in a site-specific manner in vivo. These interactions were driven by hydrophobic and electrostatic complementarity between amino acids in the peptidebinding groove of Ost3p/Ost6p and the sequestered stretch of substrate polypeptide. Based on this dependence, we used in vivo scanning mutagenesis and in vitro biochemistry to map the precise interactions that affect site-specific glycosylation efficiency. We conclude that transient binding of substrate polypeptide by Ost3p/Ost6p increases glycosylation efficiency at asparagines proximal and C-terminal to sequestered sequences. We detail a novel mode of interaction between translocating nascent polypeptide and oligosaccharyltransferase in which binding to Ost3p/Ost6p segregates a short flexible loop of glycosylation-competent polypeptide substrate that is delivered to the oligosaccharyltransferase active site for efficient modification.

DOI 10.1074/mcp.M114.041178
Citations Scopus - 6
2014 Tan NY, Bailey UM, Jamaluddin MF, Mahmud SHB, Raman SC, Schulz BL, 'Sequence-based protein stabilization in the absence of glycosylation', Nature Communications, 5 (2014)

Asparagine-linked N-glycosylation is a common modification of proteins that promotes productive protein folding and increases protein stability. Although N-glycosylation is import... [more]

Asparagine-linked N-glycosylation is a common modification of proteins that promotes productive protein folding and increases protein stability. Although N-glycosylation is important for glycoprotein folding, the precise sites of glycosylation are often not conserved between protein homologues. Here we show that, in Saccharomyces cerevisiae, proteins upregulated during sporulation under nutrient deprivation have few N-glycosylation sequons and in their place tend to contain clusters of like-charged amino-acid residues. Incorporation of such sequences complements loss of in vivo protein function in the absence of glycosylation. Targeted point mutation to create such sequence stretches at glycosylation sequons in model glycoproteins increases in vitro protein stability and activity. A dependence on glycosylation for protein stability or activity can therefore be rescued with a small number of local point mutations, providing evolutionary flexibility in the precise location of N-glycans, allowing protein expression under nutrient-limiting conditions, and improving recombinant protein production. © 2014 Macmillan Publishers Limited. All rights reserved.

DOI 10.1038/ncomms4099
Citations Scopus - 9
2013 Mohd Yusuf SNH, Bailey UM, Tan NY, Jamaluddin MF, Schulz BL, 'Mixed disulfide formation in vitro between a glycoprotein substrate and yeast oligosaccharyltransferase subunits Ost3p and Ost6p', Biochemical and Biophysical Research Communications, 432 438-443 (2013)

Oligosaccharyltransferase (OTase) glycosylates selected asparagine residues in secreted and membrane proteins in eukaryotes, and asparagine (N)-glycosylation affects the folding, ... [more]

Oligosaccharyltransferase (OTase) glycosylates selected asparagine residues in secreted and membrane proteins in eukaryotes, and asparagine (N)-glycosylation affects the folding, stability and function of diverse glycoproteins. The range of acceptor protein substrates that are efficiently glycosylated depends on the action of several accessory subunits of OTase, including in yeast the homologous proteins Ost3p and Ost6p. A model of Ost3p and Ost6p function has been proposed in which their thioredoxin-like active site cysteines form transient mixed disulfide bonds with cysteines in substrate proteins to enhance the glycosylation of nearby asparagine residues. We tested aspects of this model with a series of in vitro assays. We developed a whole protein mixed disulfide interaction assay that showed that Ost6p could form mixed disulfide bonds with selected cysteines in pre-reduced yeast Gas1p, a model glycoprotein substrate of Ost3p and Ost6p. A complementary peptide affinity chromatography assay for mixed disulfide bond formation showed that Ost3p could also form mixed disulfide bonds with cysteines in selected reduced tryptic peptides from Gas1p. Together, these assays showed that the thioredoxin-like active sites of Ost3p and Ost6p could form transient mixed disulfide bonds with cysteines in a model substrate glycoprotein, consistent with the function of Ost3p and Ost6p in modulating N-glycosylation substrate selection by OTase in vivo. © 2013 Elsevier Inc.

DOI 10.1016/j.bbrc.2013.01.128
Citations Scopus - 8
2012 Bailey UM, Jamaluddin MF, Schulz BL, 'Analysis of congenital disorder of glycosylation-id in a yeast model system shows diverse site-specific under-glycosylation of glycoproteins', Journal of Proteome Research, 11 5376-5383 (2012)

Asparagine-linked glycosylation is a common post-translational modification of proteins in eukaryotes. Mutations in the human ALG3 gene cause changed levels and altered glycan str... [more]

Asparagine-linked glycosylation is a common post-translational modification of proteins in eukaryotes. Mutations in the human ALG3 gene cause changed levels and altered glycan structures on mature glycoproteins and are the cause of a severe congenital disorder of glycosylation (CDG-Id). Diverse glycoproteins are also under-glycosylated in Saccharomyces cerevisae alg3 mutants. Here we analyzed site-specific glycosylation occupancy in this yeast model system using peptide-N-glycosidase F to label glycosylation sites with an asparagine-aspartate conversion that creates a new endoproteinase AspN cleavage site, followed by proteolytic digestion, and detection of peptides and glycopeptides by LC-ESI-MS/MS. We used this analytical method to identify and measure site-specific glycosylation occupancy in alg3 mutant and wild type yeast strains. We found decreased site-specific N-glycosylation occupancy in the alg3 knockout strain preferentially at Asn-Xaa-Ser sequences located in secondary structural elements, features previously associated with poor glycosylation efficiency. Furthermore, we identified 26 previously experimentally unverified glycosylation sites. Our results provide insights into the underlying mechanisms of disease in CDG-Id, and our methodology will be useful in site-specific glycosylation analysis in many model systems and clinical applications. © 2012 American Chemical Society.

DOI 10.1021/pr300599f
Citations Scopus - 25
2011 Jamaluddin MFB, Bailey UM, Tan NYJ, Stark AP, Schulz BL, 'Polypeptide binding specificities of saccharomyces cerevisiae oligosaccharyltransferase accessory proteins Ost3p and Ost6p', Protein Science, 20 849-855 (2011)

Asparagine-linked glycosylation is a common and vital co- and post-translocational modification of diverse secretory and membrane proteins in eukaryotes that is catalyzed by the m... [more]

Asparagine-linked glycosylation is a common and vital co- and post-translocational modification of diverse secretory and membrane proteins in eukaryotes that is catalyzed by the multiprotein complex oligosaccharyltransferase (OTase). Two isoforms of OTase are present in Saccharomyces cerevisiae, defined by the presence of either of the homologous proteins Ost3p or Ost6p, which possess different protein substrate specificities at the level of individual glycosylation sites. Here we present in vitro characterization of the polypeptide binding activity of these two subunits of the yeast enzyme, and show that the peptide-binding grooves in these proteins can transiently bind stretches of polypeptide with amino acid characteristics complementary to the characteristics of the grooves. We show that Ost6p, which has a peptide-binding groove with a strongly hydrophobic base lined by neutral and basic residues, binds peptides enriched in hydrophobic and acidic amino acids. Further, by introducing basic residues in place of the wild type neutral residues lining the peptide-binding groove of Ost3p, we engineer binding of a hydrophobic and acidic peptide. Our data supports a model of Ost3/6p function in which they transiently bind stretches of nascent polypeptide substrate to inhibit protein folding, thereby increasing glycosylation efficiency at nearby asparagine residues. © VC 2011 The Protein Society.

DOI 10.1002/pro.610
Citations Scopus - 14
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Conference (1 outputs)

Year Citation Altmetrics Link
2017 Yi-An K, Jamaluddin M, Tanwar PS, 'Extracellular Matrix (ECM) and Wnt signalling nexus in human uterine leiomyomas', Perth (2017)
Co-authors Pradeep Tanwar
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Grants and Funding

Summary

Number of grants 1
Total funding $20,000

Click on a grant title below to expand the full details for that specific grant.


20171 grants / $20,000

Mediator complex subunit 12 (MED12) gene in pathogenesis of uterine smooth muscle tumours$20,000

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Doctor Muhammad Jamaluddin, Doctor Pradeep Tanwar, Doctor Pravin Nahar
Scheme Research Grant
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1700368
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y
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Dr Muhammad Jamaluddin

Position

Lecturer
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email muhammad.jamaluddin@newcastle.edu.au
Phone (02) 4921 7476
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